Treatment-resistant obsessive-compulsive disorder (OCD) remains a significant public health problem. Despite aggressive conventional treatment, suffering and functional impairment may continue, degrading quality of life. Our three collaborative pilot studies suggest that deep brain stimulation (DBS) of the ventral anterior limb of internal capsule and adjacent ventral striatum (VC/VS) is effective in otherwise resistant OCD. The devices (made by Medtronic, Inc.) are uniquely FDA-approved for brain stimulation, with proven efficacy and safety in Parkinson disease, tremor, and dystonia. In seven years of pilot OCD work, the brain target has been refined and effective DBS parameters identified. We propose a more definitive controlled trial. This collaborative, five-year study involves the three U.S. sites most experienced in DBS for OCD, including the NIMH pilot trial site. Forty-five patients will enroll in a randomized, parallel, controlled design. We will use well-established procedures to determine if patients are resistant to medication and behavior therapies. Independent assessments of diagnosis, treatment history, and the consent process will be required for enrollment. Patients will enroll, 11-12/year, over the first four years. We will compare masked active to sham stimulation over three months to obtain primary efficacy and safety data. The criterion for DBS response will be categorical and strict: improvement in both symptoms (a 35% Yale-Brown Obsessive- Compulsive Scale score reduction) and in global functioning. After the three-month controlled phase, open DBS will continue for 1-4 years to obtain long-term effectiveness and safety data. Positron emission tomography at baseline will be used to obtain brain metabolic predictors of response. A repeat scan after at least three months of stimulation will test the hypothesis that activity in corticobasal networks implicated in OCD will change after DBS. If successful, reversible DBS will offer hope to severely affected people with few treatment options. The imaging data will provide unique insight into brain networks predicting and mediating the response to DBS for intractable OCD. [unreadable] [unreadable] [unreadable]